On August 27, 2018 CStone Pharmaceuticals (CStone) reported that its IND application for CS1002, an investigational cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) monoclonal antibody, has been approved by the China National Drug Administration (CNDA) (Press release, CStone Pharmaceauticals, AUG 27, 2018, View Source [SID1234529081]).

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"We are very pleased to obtain our third China IND approval of our investigational drugs in 2018. CStone already initiated CS1002’s Phase I clinical trial in Australia and dosed the first patient in May." said Dr. Frank Jiang, Chairman and Chief Executive Officer of CStone. " With today’s IND approval of CS1002, CStone is currently the only biopharmaceutical company in China that has all three immuno-oncology ‘backbone’ products (anti-PD-L1, anti-PD-1, and anti-CTLA-4 mAbs) in the clinical stage."

"CS1002 has demonstrated a high level of selectivity, specificity and high affinity to CTLA-4 in preclinical studies," said Dr. Jingrong Li, Senior Vice President of Product Development and Manufacture at CStone. "Combination therapies of anti-CTLA-4 mAb with anti-PD-1 mAb have demonstrated promising efficacy in multiple tumor types by global clinical trials. CStone will explore combination potentials between CS1002 and other drug candidates in our pipeline to provide better therapies for cancer patients in China and beyond."

As of today, CStone has built a portfolio of 14 oncology products, 8 of which are at clinical development stage, including 3 in registration studies. CS1001, China’s first fully human, full-length anti-PD-L1 mAb developed by CStone, has entered pivotal Phase II clinical studies, and will potentially become one of the first locally-developed anti-PD-L1 cancer drugs launched in China. In June 2018, CStone announced the exclusive collaboration and license agreements with Blueprint Medicine and Agios Pharmaceuticals. With these two deals, CStone in-licensed 4 post proof of concept assets, including ivosidenib, which is recently approved by U.S. FDA for the treatment of adult patients with relapsed or refractory acute myeloid leukemia (R/R AML) with a susceptible isocitrate dehydrogenase-1 (IDH1) mutation, and avapritinib, which has entered global Phase III clinical studies.

About the CTLA-4 pathway

Cytotoxic T lymphocyte associated antigen 4 (CTLA-4), also known as CD152, is a transmembrane protein encoded by the CTLA-4 gene that can down-regulate the activity of T cells when binding with its ligands, B7.1 and B7.2, a pathway also used by tumor cells to avoid T lymphocyte attack. Consequently, blockade of the CTLA-4 pathway can stimulate T cell activation and proliferation to induce or enhance anti-tumor immune responses. CTLA-4 provides a new immuno-therapeutic approach to a number of diseases, including tumors.

Presently, Bristol-Myers Squibb’s Yervoy (ipilimumab) is the only anti-CTLA-4 antibody to gain a market approval worldwide, although Yervoy has not yet been approved in China. Pre-clinical tests have shown that CS1002 has a relatively strong affinity to CTLA-4 and is expected to match Yervoy in terms of efficacy.

On August 27, 2018 DURECT Corporation (Nasdaq: DRRX) announced today that James E. Brown, President and CEO, will be presenting at the 20th Annual Rodman & Renshaw Global Investment Conference, sponsored by H.C. Wainwright & Co., on Thursday, September 6 at 9:10 a.m. Eastern Time (Press release, DURECT, AUG 27, 2018, http://investors.durect.com/phoenix.zhtml?c=121590&p=irol-newsArticle&ID=2364967 [SID1234529080]). The conference is being held at the St. Regis Hotel in New York City. Institutional investors and analysts that are attending the conference may request a one-on-one meeting through the conference coordinators.

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A live audio webcast of the presentation will be available by accessing View Source

A live audio webcast of the presentation will also be available by accessing DURECT’s homepage at www.durect.com and clicking "Investor Relations." If you are unable to participate during the live webcast, the call will be archived on DURECT’s website under Audio Archive in the "Investor Relations" section

On August 27, 2018 Affimed N.V. (Nasdaq: AFMD), a clinical stage biopharmaceutical company focused on discovering and developing highly targeted cancer immunotherapies that harness the power of innate and adaptive immunity (NK and T cells), reported that it has entered into a strategic collaboration agreement with Genentech, a member of the Roche Group, to develop and commercialize novel NK cell engager-based immunotherapeutics to treat multiple cancers (Press release, Affimed, AUG 27, 2018, View Source [SID1234529079]).

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Affimed will apply its proprietary Redirected Optimized Cell Killing (ROCK) platform, which enables the generation of both NK cell and T cell-engaging antibodies, to discover and advance innate immune cell engager-based immunotherapeutics of interest to Genentech. The collaboration includes candidate products generated from Affimed’s ROCK platform and multiple undisclosed solid and hematologic tumor targets. Affimed and Genentech will collaborate on the discovery, early research and late-stage research phases. Genentech will be responsible for clinical development and commercialization worldwide.

"We are incredibly excited to work with Genentech, a leader in oncology with a long history of excellence in the discovery and development of medicines to treat cancer," said Dr. Adi Hoess, Affimed’s CEO. "This strategic partnership marks an important step on our path to leverage the full potential of innate immune cells in oncology."

Under the terms of the agreement, Affimed will receive $96 million in an initial upfront payment and other near-term committed funding. Affimed may be eligible to receive up to an additional $5.0 billion over time, including payments upon achievement of specified development, regulatory and commercial milestones, and royalties on sales. The agreement is subject to customary closing conditions, including clearance under the Hart-Scott-Rodino Antitrust Improvements Act, and closing is expected to occur in the third quarter of 2018.

"This collaboration is based on Affimed’s innate immune cell drug discovery and development expertise and our team’s deep understanding of cancer immunology," commented James Sabry, M.D., Ph.D., Global Head of Partnering, Roche. "Our partnership with Affimed provides an opportunity to enhance our existing efforts to understand how the immune system can be activated to help people living with cancer."

On August 27, 2018 Kite, a Gilead Company (Nasdaq: GILD), reported that the European Commission (EC) has granted Marketing Authorization for Yescarta (axicabtagene ciloleucel) as a treatment for adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) and primary mediastinal large B-cell lymphoma (PMBCL), after two or more lines of systemic therapy (Press release, Kite Pharma, AUG 27, 2018, View Source [SID1234529078]). The Marketing Authorization approves axicabtagene ciloleucel for use in the 28 countries of the European Union, Norway, Iceland and Liechtenstein.

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Axicabtagene ciloleucel is a chimeric antigen receptor T cell (CAR T) therapy, which harnesses a patient’s own immune system to fight certain types of blood cancer. The cell therapy has been proven to induce complete response (no detectable cancer) in a proportion of patients with relapsed or refractory DLBCL and PMBCL, which are aggressive forms of non-Hodgkin lymphoma (NHL).

"Axicabtagene ciloleucel is a new and exciting way of treating cancer that offers a new option to patients with DLBCL and PMBCL in Europe," said Professor Gilles Salles, Head of Hematology, South Lyon Hospital Complex. "Many patients with these aggressive forms of non-Hodgkin lymphoma who have not responded to or failed commonly available treatment options have a very poor prognosis and there is an urgent need for new therapies."

The Marketing Authorization Application (MAA) is supported by data from the ZUMA-1 trial of axicabtagene ciloleucel in adult patients with refractory aggressive NHL. In the single-arm trial, 72 percent of patients (n=73/101) who received a single infusion of axicabtagene ciloleucel responded to therapy, with 51 percent (n=52/101) achieving a complete response (as assessed by an independent review committee, median follow-up of 15.1 months). At one year following infusion, 60 percent of patients were alive (95% CI: 50.2, 69.2) and the median overall survival (OS) had not been reached (95% CI: not estimable [NE]).

Axicabtagene ciloleucel may cause side effects that are severe or life threatening, such as cytokine release syndrome (CRS) or neurological toxicities. In ZUMA-1, 12 percent of patients experienced Grade 3 or higher CRS and 31 percent experienced Grade 3 or higher neurologic toxicities. Overall 98 percent of patients recovered from CRS and/or neurologic adverse reactions. Treatment algorithms have been developed to manage some of the symptoms associated with both CRS and neurologic adverse reactions experienced by patients on axicabtagene ciloleucel.

The most common Grade 3 or higher adverse reactions include encephalopathy, unspecified pathogen infection, CRS, bacterial infection, aphasia, viral infection, delirium, hypotension and hypertension.

For full details on the Special Warnings and Precautions for Use and Adverse Reactions (including appropriate management) please refer to the EU Summary of Product Characteristics (SmPC).

"We are proud to be leading this frontier of cancer innovation that is bringing novel, personalized therapy to people living with these blood cancers," said Alessandro Riva, MD, Gilead’s Executive Vice President, Oncology Therapeutics & Head, Cell Therapy. "Our vision is for cell therapy to serve as the foundation for treating all cancer types. Today’s milestone is another step on this exciting and important journey."

Axicabtagene ciloleucel was approved by the U.S. Food and Drug Administration on October 18, 2017.

On August 27, 2018 Bayer reported that it has filed an application for approval for larotrectinib with the European Medicines Agency (EMA) (Press release, Bayer, AUG 27, 2018, View Source [SID1234529076]). Larotrectinib has been developed for the treatment of patients (adults and children) with locally advanced or metastatic solid tumors with a fusion in the neurotrophic tyrosine receptor kinase (NTRK) genes. NTRK gene fusions are changes in the genome that result in uncontrolled production of tropo-myosin receptor kinase (TRK) receptor fusion proteins and tumor growth.

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Larotrectinib is a highly selective TRK inhibitor. It acts purposefully against TRK fusion proteins, regardless of where in the body of a patient the cancer has developed. Bayer and Loxo Oncology, a biopharmaceutical company based in Stamford, Connecticut, USA, are developing larotrectinib together. In May 2018, the US Food and Drug Administration (FDA) approved the accelerated approval process for larotrectinib in the indication "Treatment of adults and children with locally advanced or metastatic solid tumors in which a NTRK gene fusion has been detected".

"Larotrectinib has achieved significant clinical success in patients with TRK fusion tumors, and the effect has been rapid and sustained, as has been observed in various types of tumors in both adults and children," said PD. Ulrik Lassen from the oncology department of Rigshospitalet in Copenhagen.

"The approval of larotrectinib would be a paradigm shift in cancer treatment, targeting the change in the genome that promotes cancerous growth, regardless of where in the body the cancer occurred." Scott Fields, Senior Vice President and Head of Oncology Development at Bayer. "The approval application for larotrectinib brings us one step closer to our goal of providing a much-needed treatment option in Europe for cancer patients with TRK fusion tumors."

About Larotrectinib (LOXO-101)
Larotrectinib (LOXO-101) is a potent, orally-to-be, selectively-acting new investigational drug currently in clinical development for the treatment of patients with a variety of cancers that have tropomyosin receptor kinase (TRK) abnormalities. play a role. Numerous studies suggest that the neurotrophic tyrosine receptor kinase genes (NTRK genes), which code for TRK and normally have major functions in the nervous system, may undergo abnormal fusions with other genes. This leads to growth signals that can cause cancer in numerous other areas of the body.

In clinical studies with patients presenting various types of solid tumors with NTRK gene fusions, larotrectinib showed an investigator-determined overall response rate (ORR) of 80 percent and an ORR of 75 percent, as confirmed by independent review. Larotrectinib was well tolerated with most of the adverse events reported being grade 1 or 2.

In November 2017, Bayer and Loxo Oncology announced that they would jointly develop and market the active ingredients larotrectinib and LOXO-195, another novel TRK inhibitor. Outside the US, Bayer will oversee regulatory activities and global marketing activities. Bayer and Loxo Oncology will jointly distribute the product in the United States. Loxo Oncology remains responsible for ongoing clinical trials and regulatory activities in the United States.

More information about the clinical trials with Larotrectinib or LOXO-195 can be found at www.clinicaltrials.gov or on the website www.loxooncologytrials.comavailable. Larotrectinib and LOXO-195 are not approved by the US Food and Drug Administration (FDA), the European Commission or other health authorities.

About TRK fusion cancer
TRK fusion cancer is due to NTRK gene fusions. These are chromosomal mutations that occur when one of the neurotrophic tyrosine receptor kinase (NTRK) genes binds abnormally to another, non-contiguous gene and results in an aberrant NTRK gene. The translated abnormal protein, or TRK fusion protein, is continuously active and this can lead to uncontrolled and possibly cancer-causing cell communication. These proteins are the major driver for the development and spread of tumors in patients with TRK fusion tumors. TRK fusion tumors can occur anywhere in the body because they are not bound to specific cell or tissue types. NTRK gene fusions occur in a variety of solid tumors in both adults and children. These include carcinoma of the appendix, breast cancer, bile duct carcinoma, colon cancer, GIST (gastrointestinal stromal tumors), fibrosarcoma in children, lung cancer, mammary analogue secretory carcinoma (MASC) of the salivary glands, melanoma, pancreatic cancer, thyroid cancer and various sarcomas. A TRK fusion tumor can only be diagnosed using sensitive and specific tests. Next generation sequencing (NGS) can provide a comprehensive view of the genomic changes in a variety of genes. Fluorescence in situ hybridization (FISH) and polymerase chain reaction (PCR) -based assays, on the other hand, are more suitable for highly targeted analysis because of their lower multiplex ability, while immunohistochemistry (IHC) is based on detection of the TRK protein.trkcancer.com/.

About Oncology at Bayer With the goal of improving people’s lives, Bayer is working to expand its portfolio of innovative treatments. Bayer’s Oncology division includes four approved compounds as well as other compounds in various stages of clinical development. All of these products reflect the company’s research approach, which focuses on the search for appropriate cancer targeting targets.